Guaifenesin

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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C₁₀H₁₄O₄ 198.22

1,2-Propanediol, 3-(2-methoxyphenoxy)-(±)-;

(±)-3-(o-Methoxyphenoxy)-1,2-propanediol CAS RN®: 93-14-1; UNII: 495W7451VQ.

1 DEFINITION

Guaifenesin contains NLT 98.0% and NMT 102.0% of guaifenesin (C₁₀H₁₄O₄), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197A or 197K (CN 1-May-2020)

Change to read:

B. Spectroscopic Identification Tests 〈197〉, Ultraviolet-Visible Spectroscopy: 197U (CN 1-May-2020)

Sample solution: 40 μg/mL in methanol

Acceptance criteria: Meets the requirements

3 ASSAY

3.1 Procedure

Solution A: Glacial acetic acid and water (1:99)

Solution B: Acetonitrile

Mobile phase: See Table 1.

Table 1

System suitability solution: 0.5 mg/mL of USP Guaifenesin RS and 0.02 mg/mL of USP Guaiacol RS in Solution B

Standard solution: 0.5 mg/mL of USP Guaifenesin RS in Solution B

Sample solution: 0.5 mg/mL of Guaifenesin in Solution B

3.2 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 276 nm

Column: 4.6-mm × 25-cm; 5-μm packing L1

Flow rate: 1 mL/min

Injection volume: 10 μL

3.3 System suitability

Samples: System suitability solution and Standard solution

[Note - See Table 2 for relative retention times.]

3.4 Suitability requirements

Resolution: NLT 3 between guaifenesin and guaiacol, System suitability solution

Relative standard deviation: NMT 1.0%, Standard solution

3.5 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of guaifenesin (C₁₀H₁₄O₄) in the portion of Guaifenesin taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of guaifenesin from the Sample solution

r_S = peak response of guaifenesin from the Standard solution

C_S = concentration of USP Guaifenesin RS in the Standard solution (mg/mL)

C_U = concentration of Guaifenesin in the Sample solution (mg/mL)

To this value, add the percentage of guaifenesin β-isomer found in the test for Organic Impurities.

Acceptance criteria: 98.0%–102.0% on the dried basis

4 IMPURITIES

Change to read:

Organic Impurities

Solution A, Solution B, Mobile phase, System suitability solution, Standard solution, Chromatographic system, and System suitability: Proceed as directed in the Assay.

Sample solution: 2 mg/mL of Guaifenesin in Solution B

Diluted sample solution: 0.02 mg/mL of Guaifenesin from the Sample solution in Solution B

Analysis

Samples: Sample solution and Diluted sample solution

[Note - See Table 2 for relative retention times.]

[Note - All of the peaks are baseline resolved.]

Calculate the percentage of each individual impurity in the portion of Guaifenesin taken:

Result = (r_U/r_S) × (C_S/C_U) × (1/F) × 100

r_U = peak response of each individual impurity from the Sample solution

r_S = peak response of guaifenesin from the Diluted sample solution

C_S = concentration of guaifenesin in the Diluted sample solution

C_U = concentration of guaifenesin in the Sample solution (ERR 1-Nov-2018)

F = relative response factor

Acceptance criteria: See Table 2.

Table 2

^a 2-(2-Methoxyphenoxy)-1,3-propanediol.

^b Excluding guaifenesin β-isomer and guaiacol.

5 SPECIFIC TESTS

Loss on Drying 〈731〉

Analysis: Dry under vacuum (NLT 10 mm of mercury) at 60° to a constant weight.

Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers.

USP Reference Standards 〈11〉

USP Guaiacol RS

USP Guaifenesin RS